Lower Plasma Total Cholesterol Research Articles

Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E −/− mice

The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E −/− mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E −/− mice.

Efficacy of a plant sterol‐fortified low fat soy beverage on cholesterol metabolism in normal to mildly‐hypercholesterolemic subjects

The objective of this study was to evaluate the efficacy of plant sterol‐enriched low‐fat soy milk (PS‐LS) on lipid levels in individuals with normal to elevated low density lipoprotein‐cholesterol (LDL‐C) levels, compared to 1% dairy milk (DM). Thirty‐three subjects (LDL‐C >2.1 mmol/L) were fed a controlled low fat diet supplemented with DM or PS‐LS providing 1.95 g of PS/d, using a cross‐over study. Each dietary phase was 4 wk in duration, separated by a 4 wk wash‐out period. Blood samples were taken at the beginning and the end of each phase. Consumption of PS‐LS lowered (P<0.0001) plasma total cholesterol (T‐C) levels by 10%, compared to DM feeding (5.26±0.16 vs 5.80±0.17 mmol/L). A 13% reduction (P<0.0001) in plasma LDL‐C levels was observed following PS‐LS consumption, relative to DM intake (3.20±0.15 vs 3.66±0.15 mmol/L). Compared to the DM control, PS‐LS supplementation lowered T‐C/HDL‐C (P=0.0011) and LDL‐C/HDL‐C (P=0.0008) ratios (T‐C/HDL‐C=4.71±0.27 and 5.05±0.26 for PS‐LS and DM, respectively; LDL‐C/HDL‐C=2.74±0.20 and 3.21±0.20 for PS‐LS and DM, respectively). Results promote the use of PS‐LS as an effective functional food, which may exert more profound cardio‐protective effects, compared to the choice of DM, in normal and hypercholesterolemic populations. Sponsored by WhiteWave Foods Company.

The dual PPARα/γ agonist tesaglitazar blocks progression of pre‐existing atherosclerosis in APOE*3Leiden.CETP transgenic mice

We have evaluated the effects of a peroxisome proliferator-activated receptor (PPAR)alpha/gamma agonist on the progression of pre-existing atherosclerotic lesions in APOE*3Leiden.cholesteryl ester transfer protein (E3L.CETP) transgenic mice. E3L.CETP mice were fed a high-cholesterol diet for 11 weeks to induce atherosclerosis, followed by a low-cholesterol diet for 4 weeks to obtain a lower plasma total cholesterol level of approximately 10 mmol.L(-1). Mice were divided into three groups, which were either killed before (baseline) or after an 8 week treatment period with low-cholesterol diet without (control) or with the PPARalpha/gamma agonist tesaglitazar (10 microg.kg(-1).day(-1)). Atherosclerosis was assessed in the aortic root. Treatment with tesaglitazar significantly reduced plasma triglycerides, total cholesterol, CETP mass and CETP activity, and increased high-density lipoprotein-cholesterol. At baseline, substantial atherosclerosis had developed. During the 8 week low-cholesterol diet, atherosclerosis progressed in the control group with respect to lesion area and severity, whereas tesaglitazar inhibited lesion progression during this period. Tesaglitazar reduced vessel wall inflammation, as reflected by decreased monocyte adhesion and macrophage area, and modified lesions to a more stabilized phenotype, with increased smooth muscle cell content in the cap and collagen content. Dual PPARalpha/gamma agonism with tesaglitazar markedly improved the atherogenic triad by reducing triglycerides and very low-density lipoprotein-cholesterol and increasing high-density lipoprotein-cholesterol and additionally reduced cholesterol-induced vessel wall activation. These actions resulted in complete inhibition of progression and stabilization of pre-existing atherosclerotic lesions in E3L.CETP mice.

대두박 사포닌 보충이 식이성 유도 비만마우스의 체중과 내당능에 미치는 영향

본 연구는 폐기되는 대두박으로부터 분리한 사포닌이 고지방식이로 유도한 비만마우스의 체중, 지질 함량, 지질대사 및 내당능에 미치는 영향을 살펴보았다. 4주령의 C57BL/6 마우스(n=48)를 1주일간 적응시킨 후 정상식이를 급여한 정상군, 고지방을 급여한 고지방대조군, 고지방식이에 대두박 사포닌을 수준별(0.5%, 1.0%, 1.5%, w/w)로 급여한 군들과 양성대조물질인 가르시니아 캄보지아(1.0%, w/w)를 급여한 군으로 나누어 9주간 사육하였다. 체중증가량과 내장지방(부고환 지방과 신장주변 지방) 무게는 고지방대조군에 비하여 대두박 사포닌 급여 수준에 의존적으로 낮아졌다. 캄보지아는 식이섭취량을 억제시킨 반면, 대두박 사포닌은 비만 유도 마우스의 식이섭취량에 유의적인 영향을 미치지 않았다. 혈장 중의 렙틴 함량은 고지방대조군에 비하여 대두박 사포닌 보충군에서 낮았다. 대두박 사포닌 급여수준에 관계없이 혈장의 중성지질과 총 콜레스테롤 함량은 유의적으로 낮아진 반면, 사포닌 급여 수준에 의존적으로 변으로 중성지질 배설은 유의적으로 높았다. 한편, 캄보지아는 변의 지질함량에 유의적인 영향을 미치지 않았다. 간조직 중의 중성지방과 콜레스테롤 함량 역시 고지방대조군에 비하여 대두박 사포닌 급여군(1.5%)에서 유의적으로 개선되었으나 캄보아지군의 콜레스테롤 함량은 증가되었다. 고지방식이는 정상식이에 비하여 혈당과 내당능을 유의적으로 증가시켰으나 대두박 사포닌과 캄보지아 급여는 혈당과 식후 혈당 변화를 효과적으로 개선하는 것으로 나타났다. 특히, 1.5% 대두박사포닌 급여군의 혈당은 정상군 수준이었다. 9주 동안 고지방식이 급여는 간조직 중의 지방산 합성과 산화효소활성을 모두 증가시켰는데 합성효소의 상승이 훨씬 큰 것으로 나타났다. 그러나 대두박 사포닌은 간조직 중의 지방산 합성과 산화효소활성을 정상화하였다. 이와 같이 대두박 사포닌은 비만유도 마우스에서 변으로의 중성지질 배설을 증가시키고 간조직에서 지질대사 관련 효소활성을 조절함으로써 체중조절과 혈당개선에 효과적이었다.

Phytosterol Intake and Dietary Fat Reduction are Independent and Additive in their Ability to Reduce Plasma LDL Cholesterol

We studied the interrelationship of diet and plant sterols (PS) on plasma lipids, lipoproteins and carotenoids. Mildly hypercholesterolemic men (n = 13) and postmenopausal women (n = 9) underwent four randomized, crossover, double-blind, controlled feeding periods of 23 days each. The design consisted of two levels of PS (0 and 3.3 g/day) and two background diets having fat content either typical of the American diet (total and saturated fat at 33.5 and 13.2% of energy, respectively), or a Step 1 type of diet (total and saturated fat at 26.4 and 7.7% of energy, respectively). Plasma total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A1 and Apo B were 4.3, 5.3, 4.5, 2.8 and 2.5% lower, respectively (P <or= 0.0001; <0.0001, 0.0016, 0.0006, and 0.0069), with the Step 1 diet than with the typical American diet. Diet had no effect on TC/HDL cholesterol (P = 0.1062). Plant sterol intake lowered TC, LDL cholesterol, and Apo B by 9.0, 12.4 and 6.1% and TC/HDLC by 9.6% (P <or= 0.0001 for all), respectively, without affecting HDL cholesterol and Apo A1 (P = 0.2831 and 0.732). The PS effect in lowering plasma TC and LDL cholesterol was independent of and additive to the effect due to dietary fat reduction. Responses of plasma carotenoids to PS intake were consistent with the literature.

Anti-Diabetic and Anti-Lipidemic Activities of Metformin-Ascorbic Acid Combination

The present study was designed to investigate the pharmacological effects of metformin-ascorbic acid combination on glycemic and lipids control in glucose-induced insulin resistance rats and elucidate its possible mechanism(s) of action. The anti-hyperglycemic and anti-lipidemic activities of metformin, ascorbic acid, and metformin-ascorbic acid combination were studied in 5 groups consisting of 6 rats per group and weighing 100-130 g, by administering daily oral dosing of 20 g/kg of D - glucose in addition to 10 ml/kg of water, 10, 20 and 30 mg/kg/day of the drugs, respectively, for 42 days. Results of the study showed that metformin and metformin-ascorbic acid combination induced significant and comparable anti-hyperglycemia. This effect was mediated through enhanced sensitivity of peripheral tissues to insulin action. Metformin-ascorbic acid also lowered plasma total cholesterol, LDL-cholesterol (LDL-c), VLDL-cholesterol (VLDL-c) significantly. The results of this study suggest that the drug combination has antidiabetic and anti-lipidemic effects and therefore, could be a novel combination in the management of type 2 diabetes mellitus patients. Keywords: Metformin-ascorbic acid combination, fasting plasma glucose and lipids, glucose-induced insulin resistanceWest African Journal of Pharmacology and Drug Research Vol. 22/23 2007: pp. 10-15

Coenzyme Q10: An Independent Predictor of Mortality in Chronic Heart Failure

The aim of this study was to investigate the relationship between plasma coenzyme Q(10) (CoQ(10)) and survival in patients with chronic heart failure (CHF). Patients with CHF have low plasma concentrations of CoQ(10), an essential cofactor for mitochondrial electron transport and myocardial energy supply. Additionally, low plasma total cholesterol (TC) concentrations have been associated with higher mortality in heart failure. Plasma CoQ(10) is closely associated with low-density lipoprotein cholesterol (LDL-C), which might contribute to this association. Therefore we tested the hypothesis that plasma CoQ(10) is a predictor of total mortality in CHF and could explain this association. Plasma samples from 236 patients admitted to the hospital with CHF, with a median (range) duration of follow-up of 2.69 (0.12 to 5.75) years, were assayed for LDL-C, TC, and total CoQ(10). Median age at admission was 77 years. Median (range) CoQ(10) concentration was 0.68 (0.18 to 1.75) micromol/l. The optimal CoQ(10) concentration for prediction of mortality (established with receiver-operator characteristic [ROC] curves) was 0.73 micromol/l. Multivariable analysis allowing for effects of standard predictors of survival--including age at admission, gender, previous myocardial infarction, N-terminal peptide of B-type natriuretic peptide, and estimated glomerular filtration rate (modification of diet in renal disease)--indicated CoQ(10) was an independent predictor of survival, whether dichotomized at the ROC curve cut-point (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.2 to 3.3) or the median (HR: 1.6; 95% CI: 1.0 to 2.6). Plasma CoQ(10) concentration was an independent predictor of mortality in this cohort. The CoQ(10) deficiency might be detrimental to the long-term prognosis of CHF, and there is a rationale for controlled intervention studies with CoQ(10).

Abdominal localization of Tangier disease mimicking a pancreatic neoplasm

Tangier disease is a rare genetic disorder of lipid metabolism, characterized by severe deficiency of plasma high-density lipoprotein cholesterol, low-plasma total cholesterol, and accumulation of cholesteryl ester in macrophages. Abdominal manifestation of Tangier disease is extremely rare, being reported only once in the English literature. We describe a 55-year-old patient with this condition, who underwent splenectomy 37 years before, because of splenomegaly with thrombocytopenia, and subsequently presented with abdominal pain and pancreatic mass, simulating a pancreatic tumor. The preoperative diagnosis of endocrine or solid-cystic neoplasm was made, and the tumor was successfully resected with distal pancreatectomy. Histological examination showed that the mass was composed of histiocytic cells containing lipids; some aggregates of giant polynucleated histiocytes with intracytoplasmic cholesterol crystals. To our knowledge, this is the first report of pancreatic manifestation of Tangier disease. As suggested earlier, splenectomy in these patients seems to predispose to deposition of lipids and infiltration of the abdomen by inflammatory cells.

Cholesterol-Lowering Nutraceuticals and Functional Foods

Epidemiological studies have demonstrated that elevated levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the major risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) and a low ratio of TC to HDL-C are protective against CHD. A relationship between plasma TC and the risk of CHD is well established at concentrations above 240 mg/dL. In addition to the use of three main classes of cholesterol-lowering medications, including HMG-CoA reductase inhibitors, anion-exchange resins, and fibrates, a nutritionally balanced diet that reduces saturated fat and cholesterol intake has traditionally been the first goal of dietary therapy in lowering plasma TC. In recent years, nutraceuticals and functional foods have attracted much interest as possible alternative therapies for lowering plasma TC, especially for hypercholesterolemia patients, whose blood cholesterol level is marginally high (200-240 mg/dL) but not high enough to warrant the prescription of cholesterol-lowering medications. This review summarizes the findings of recent studies on the production, application, efficacy, and mechanisms of popular cholesterol-lowering nutraceuticals and functional foods.

Effects of Simultaneous Intakes of Fish Oil and Green Tea Extracts on Plasma, Glucose, Insulin, C-Peptide, and Adiponectin and on Liver Lipid Concentrations in Mice Fed Low- and High-Fat Diets

Aims: The purpose of this study was to clarify the effects of a simultaneous intake of fish oil and green tea extracts (GTE) on plasma lipids, glucose (Glu), insulin, C-peptide, and adiponectin concentrations and on liver lipids in mice fed low- and high-fat diets. Methods: Male mice (5 months old) were fed low-fat (5%) or high-fat (20%) diets containing 0% (5 or 20% lard), 1% (4 or 19% lard) or 5% (0 or 15% lard) fish oil with or without 1% GTE for 3 months. Results: Single or combined intakes of fish oil and GTE intakes significantly lowered plasma and liver total cholesterol (T-chol) and triacylglycerol (TG) concentrations in mice on high-fat diets. However, a positive effect of GTE alone was not observed in the plasma T-chol and TG concentrations of mice on low-fat diets. Plasma Glu concentrations were significantly lowered by dietary fish oil in mice on the low- and high-fat diets. A tendency of GTE intake to decrease plasma Glu in mice on both the low- and high-fat diets was not significant. An intake of GTE only minimally influenced plasma insulin, C-peptide, and adiponectin concentrations, but fish oil supplementation increased the adiponectin concentration in mice on the low- and high-fat diets. GTE addition to the diets had no adverse effects on reductions by fish oil. Conclusion: These results suggest that a simultaneous intake of fish oil and GTE can improve plasma and liver lipid and plasma Glu profiles in mice fed a high-fat diet without any negative interactions of fish oil and GTE.

Efficacy of plant sterols in novel matrices on blood lipid profiles: medium-chain triglycerides and low-fat products consumed with or without a meal

Cardiovascular disease (CVD) risk can be lowered by introduction of plant sterols (PSs) to the diet, since PSs have been shown to reduce low-density lipoprotein cholesterol (LDL-C). Given that the efficacy of PSs as cholesterol-lowering agents depends on their appropriate solubilization, the cholesterol-lowering efficacy of PSs in non-traditional matrices needs to be determined. The primary aim of this thesis was to examine the consumption of PSs (i) in an oil that is rich in medium-chain triglycerides (MCTs) or (ii) low-fat yogurt with or without a meal, on changes in lipid parameters. Additional objectives were to assess the effects of MCTs with PSs on body composition and energetics, to compare the effects of PSs in a low-fat matrix consumed with or without a meal on cholesterol synthesis, to evaluate the risks of PSs in a low-fat matrix on blood levels of carotenoids and fat-soluble vitamins, and to investigate the relationship between the response to PSs, cholesterol kinetics, and genotyping. For this purpose, two randomized, controlled, crossover feeding trials were conducted. First, 23 overweight, hyperlipidemic men consumed PSs in MCTs or an olive oil control for 6 weeks each. In the second trial, 26 hyperlipidemic subjects consumed a placebo yogurt, a PS-enriched yogurt consumed with a meal, or afternoon PS-enriched yogurt as a snack for 4 weeks each. PSs, mixed within an MCT matrix, lowers plasma total cholesterol (TC) and LDL-C without changing the high-density lipoprotein cholesterol concentrations. However, no changes in body composition or energetics were observed. Second, a PS-enriched low-fat yogurt as a snack lowered TC, along with a lowering trend in LDL-C, to a greater extent than when consumed with a meal without any risk of deficiency in fat-soluble antioxidants. An increase in cholesterol biosynthesis was also observed in both PS phases compared with the control phase. In addition, 3 subjects who were non-responsive to PS intervention and had higher cholesterol absorption rates were observed; however, no recognizable pattern of genetic polymorphism was detected. Overall, these novel matrices for PS incorporation consumed with or between meals may be an effective way of decreasing the risk of CVD; however, some individuals respond better to PS intervention.

Rye bread reduces plasma cholesterol levels in hypercholesterolaemic pigs when compared to wheat at similar dietary fibre level

AbstractBACKGROUND: Rye is a whole‐grain cereal with the potential of contributing to a healthy diet, but research on rye in relation to chronic diseases is scarce compared to wheat and oats. In this study, a total of 17 hypercholesterolaemic pigs were fed high‐fat high‐cholesterol rye (n = 9) or wheat‐based buns (n = 8) with similar dietary fibre (DF) content for 9–10 weeks to study the effect on cardiovascular risk factors.RESULTS: Ingestion of rye bread resulted in a 40% lower plasma total and LDL cholesterol compared to the wheat group, whereas HDL cholesterol, insulin and glucose concentrations were not affected by dietary treatments. Intestinal viscosity was 7.2 times higher, and organic matter and fat digestibility significantly reduced in the pigs fed rye buns. The hepatic expression of the cholesterol 7α‐hydroxylase gene (CYP7A1) was lower in rye‐fed pigs, whereas four other key genes involved in cholesterol metabolism were not affected. Plasma cholesterol correlated inversely with intestinal viscosity and organic matter digestibility.CONCLUSION: The ability of DF from rye to interfere with digestion and absorption is more important for whole‐body cholesterol homeostasis than regulation in the liver at gene level. Copyright © 2008 Society of Chemical Industry

Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats

The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague–Dawley rats. Four groups of animals were fed a cornstarch–casein–sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100 mg kg −1 body weight d −1), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% ( p = 0.067) and non-HDL-cholesterol (non-HDL-C) by 29% ( p = 0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% ( p = 0.0002) and non-HDL-C by 59% ( p < 0.0001) compared to the control group. BBR reduced plasma TG levels by 31% at a marginal significance relative to the control ( p = 0.054), whereas PS had no effect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol ( p = 0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects.

Myeloperoxidase gene sequence variations are associated with low-density-lipoprotein characteristics

The small, dense low-density-lipoprotein (LDL) phenotype is associated with an increased atherosclerosis risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus (QTL) for LDL peak-particle size (LDL-PPD) on the 17q21 region. This region encodes the myeloperoxidase (MPO) gene. MPO is able to oxidize LDL by its reactive intermediates. To test the associations between MPO gene polymorphisms and LDL-PPD as well as plasma lipid levels, we performed direct sequencing of the coding regions, exon-intron splicing boundaries, and the regulatory regions on 25 subjects to identify new genetic variants. Genotyping was performed either by TaqMan or direct sequencing on 680 subjects in the QFS. LDL-PPD was measured by gradient gel electrophoresis (GGE) on nondenaturing 2-16% polyacrylamide gradient gels. MPO gene sequencing revealed 16 polymorphisms. The c.-653G > A MPO polymorphism was associated with lower plasma total cholesterol, LDL cholesterol (LDL-C), and LDL apolipoprotein B (LDL-apoB) levels (P = 0.026, 0.042 and 0.014, respectively). No significant association with a gene-dosage effect were observed for LDL-PPD. The MPO gene variants are not associated with LDL-PPD and thus are unlikely to be responsible for the quantitative trait locus reported on 17q21. However, the c.-653G > A is associated with plasma LDL-C and LDL-apoB concentrations.

Anti-Obesity and Hypolipidemic Effects of a Proprietary Herb and Fiber Combination (S&amp;S PWH) in Rats Fed High-Fat Diets

The objective of this study was to investigate the effects of S&S PWH, a proprietary herb and fiber combination (Bionutrigen Inc., Daejon, Republic of Korea), on body weight and lipid metabolism in rats fed with a high-fat diet. Three groups of male Sprague-Dawley rats were fed different diets for a 6-week period: normal control diet containing 5% (wt/wt) corn oil (NC group), high-fat diet containing 10% (wt/wt) lard plus 5% (wt/wt) corn oil (HF group), and high-fat diet supplemented with powdered 5% (wt/wt) S&S PWH (S&S PWH group). The body weights and relative weights of the epididymal and perirenal white adipose tissue were significantly lower in the S&S PWH group than in the HF group. S&S PWH supplementation significantly lowered plasma total cholesterol and triglyceride concentrations, whereas it elevated the ratio of high density lipoprotein-cholesterol/total-cholesterol and improved the atherogenic index. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size were less in the S&S PWH group than in the HF group. Hepatic hydroxyl-3-methylglutaryl-coenzyme A reductase and acyl-coenzyme A:cholesterol acyltransferase activities were significantly lower, while adipocyte lipoprotein lipase activity was significantly higher, in the S&S PWH group than in the HF group. These beneficial effects may be due to the combined properties of the phenolic compounds present in high concentrations (1.89 g/100 g) in the S&S PWH. In conclusion, these results suggest that S&S PWH can be considered as an anti-obesity functional formula that is effective for suppressing body weight gain and enhancing lipid profile.

Lipid Lowering Effect of Antioxidant Alpha-Lipoic Acid in Experimental Atherosclerosis

Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction of lipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a dual lipid lowering and anti-atherosclerotic properties indicated with low plasma TC and LDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits.

Lipolytic and Hypolipidemic Properties of Newly Synthesized Aryloxypropanolamine Derivatives

In this study, the lipolytic effect of two newly synthesized potential β3-adrenergic agonists A482 and B496 in active acid forms was tested using isolated sliced epididymal adipose tissue of Wistar rats, and compared with Isoprenaline and BRL37344. Furthermore, effects of an eight-week oral administration of the newly synthesized substances on serum cholesterol, triglycerides, glucose, adiponectin, resistin and weight gain were studied in C57Bl/6J mice that were fed high energy diet. The newly synthesized substance A482 (4-(2-{[2-hydroxy-3-(4-methyl-carbamoylphenoxy) propyl]amino}ethyl)phenoxy-acetic acid hydrochloride) was able to produce almost full lipolysis at a 1 × 10-7 M concentration, and its effect on the rat epididymal adipose tissue was similar to the specific β3-adrenergic agonist BRL37344. Ethyl ester of this substance significantly lowered plasma total cholesterol (p &lt; 0.001), resistin (p &lt; 0.01), weight gain (p &lt; 0.01), improved total/HDL-cholesterol ratio (p &lt; 0.01) and increased circulating adiponectin (p &lt; 0.001) in C57Bl/6J mice that were fed high energy diet. The second tested substance B496 did not show all activities expected from β3-adrenergic agonists. Our results suggest that the newly synthesised substance A482 may represent a potent β3-adrenergic agonist.

Isoflavone Glycitein Diminished Plasma Cholesterol in Female Golden Syrian Hamsters

The soybean isoflavones, daidzein, genistein, and glycitein, were hypothesized to act as cholesterol-lowering components, separate from soy protein. Pure synthetic daidzein, genistein, or glycitein (0.9 mmol/kg diet) or a casein-based control diet was fed to groups of 10 female Golden Syrian hamsters for 4 weeks. Hamsters fed glycitein had significantly lower plasma total (by 15%) and non-HDL (by 24%) cholesterol compared with those fed casein (P<0.05). Daidzein and genistein's effects on these lipids did not differ from the effects of either casein or glycitein. Plasma HDL cholesterol and triglyceride concentrations were not significantly affected by dietary treatments. The percentage of urinary recovery of the ingested dose of each isoflavone was glycitein>daidzein>genistein (33.2%, 4.6%, 2.2%, respectively), with the apparent absorption of glycitein significantly greater than that of the other isoflavones. These data suggest that glycitein's greater cholesterol-lowering effect was due to its greater bioavailability, as reflected in its urinary recovery compared with that of the other isoflavones.

Low plasma total cholesterol in patients with Huntington’s disease and first-degree relatives

Recent studies indicate altered cholesterol homeostasis in Huntington’s disease (HD) after it was found that cultured human and mice cells expressing mutant huntingtin show reduced mRNA of cholesterol biosynthetic enzymes. Plasma total cholesterol (TC) levels have been connected to degenerative disorders, but data for HD are lacking. We estimated plasma TC in three groups of HD related subjects: (a) patients with overt symptomatology, (b) subjects with expanded CAG repeat number in the Huntington gene before disease onset, and (c) siblings or descendants of HD patients, with normal CAG repeat number. Compared to TC levels of age-matched controls, all three groups had significantly lower plasma TC levels. The expected positive correlation of TC to age, present in the control group, was absent in the whole group or the three subgroups of the HD subjects. TC of the ApoE genotype subgroups showed small, non-significant differences. In the group of patients, TC levels were not related to severity of illness, duration of illness, and presence of depression or dementia in their symptomatology, while lower TC levels were found in patients with psychotic features. The results indicate altered cholesterol homeostasis in members of families with HD patients. Low TC levels have been connected to increased suicide risk in several studies, and high suicidal ideation has been reported in both HD gene carriers and non-carriers. Although low plasma TC levels do not necessarily imply alterations in brain cholesterol levels, a more detailed study of plasma lipids in HD patients and their first-degree relatives, as well as the search for genetic factors regarding cholesterol synthesis and disposition, are warranted.

Soybean Protein Hydrolysate Improves Plasma and Liver Lipid Profiles in Rats Fed High-Cholesterol Diet

Objective: This investigation attempted to clarify the hypolipidemic effects of non-dialyzed soybean protein hydrolysate (NSPH), which is hydrolyzed by pepsin from soybean acid-precipitated protein (APP), in rats fed a cholesterol-rich diet.Methods: Forty Sprague-Dawley rats were divided into four groups as the control group (19.7% casein), the APP group (14.7% casein + 5% APP), the NSPH group (14.7% casein + 5% NSPH), and the ISO group (19.7% casein + 0.0013% soy isoflavone).Results: After 12-week experimental period, the APP and NSPH groups had a significant lower plasma total cholesterol, triglycerides, and LDL-cholesterol concentrations compared with the control group. Additionally, the atherosclerosis index in APP and NSPH group had also markedly decreased. Liver cholesterol and triglyceride contents of the APP and NSPH group were significantly lower than those of the control group. There were no different in plasma LDL-C, liver cholesterol and triglycerides between the ISO group and control group. Fecal excretion of neutral steroids and nitrogen compounds was significantly higher in the APP and NSPH groups than that in the control group. An in vitro study also showed that NSPH, compared with casein, obviously decreased cholesterol micellar solubility.Conclusion: These results suggested that NSPH may decrease lipid accumulation in the liver and have a hypolipidemic effect by enhancing excretion and inhibiting absorption of lipids.